ChEMBL

On December 31 2012, the FDA approved Crofelemer for the treatment of diarrhea caused by antiretroviral medication regimens taken by patients with HIV/AIDS.

Diarrhea is a frequent adverse effect of antiretroviral medication - however, it can also be caused by secondary infections of the gastrointestinal tract or the virus itself. The loss of fluids incurred by diarrhea can lead to dehydration and electrolyte imbalance. As a side-effect of antiretroviral medication it also reduces patient compliance with a prescribed medication regimen.

Crofelemer alleviates the symptoms of HIV-associated diarrhea by limiting the amount of chloride ions that are pumped into the intestinal lumen, thus also retaining sodium ions and water. Crofelemer is a natural product oligomer that is not orally bioavailable but acts locally on the intestinal surface. It was shown to inhibit two distinct intestinal chloride channels expressed in the luminal membrane of gut epithelial cells. One of them, the cystic fibrosis transmembrane conductance regulator (CFTR, Uniprot: P13569, CHEMBL4051) is a member of the ABS transporter family, the other is a calcium-activated chloride channel (CaCC) and is called Anoctamin-1 (TMEM16A, Uniprot: Q5XXA6). Anoctamin-1 is currently the only known CaCC expressed at the luminal membrane of gut epithelial cells but crofelemer might also inhibit other CaCCs.


Crofelemer is extracted from the red latex of the South American tree Croton lechleri and is an amorphous red-brown powder. The oligomer is a random sequence of (+)-catechin, (-)-epicatechin, (+)gallocatechin and (-)-epigallocatechin monomers (on average 5 to7.5) and average mass of 1500Da to 2300Da.

Crofelemer is dosed twice-daily in delayed release tablets containing 125mg of the active ingredient. It is practically not absorbed into the blood and typical pharmacokinetic parameters are thus not applicable.

Crofelemer was initially developed by Shaman Pharmaceuticals and then continued by Napo Pharmaceuticals (Forbes has a short article on Crofelemer's development). At the moment, Salix Pharmaceuticals holds a license for marketing in Japan, North America and Europe while Glenmark Pharmaceuticals has exclusive rights to marketing in 140 developing countries including India (but excluding China).

The commercial name for crofelemer is Fulyzaq.